Cyclic AMP (cAMP) in mammalian cell functions by binding to cAMP receptor protein, the regulatory subunit of cAMP- dependent protein kinase. The cAMP receptor protein has two different cAMP binding sites, and cAMP analogs that specifically bind to either one of the two binding sites are known as Site 1- selective (C-2 and C-8 analogs) and Site 2-selective (C-6 analogs), respectively. Further the Site-1 and Site 2-selective analogs in combination produce synergistic enhancement of the binding to cAMP receptor protein and protein kinase activation in vitro. Application of these in vitro findings to demonstrate cAMP analog-mediated response in vivo, in intact cells or tissues has been scarce. Moreover, virtually all past studies of cAMP- regulation of cell growth employed a few, early known, cAMP analogs with are weakly active for protein kinase and effective only at unphysiological high mM concentrations. The site- selective cAMP analogs which are many-fold more active for protein kinase have never been tested for their growth regulatory effect. We, therefore, investigated the growth regulatory effect of site- selective cAMP analogs on a spectrum of human cancer cell lines and the in vivo growth of rodent mammary tumors. The analog effect on the cell growth will be correlated with the response of cAMP receptor protein present in the cancer cells. The goal of this study is to elucidate the growth regulatory mechanism of cAMP analogs which can be extrapolated to the treatment of human cancer.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005216-17
Application #
3939260
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code